The role of alveolar macrophages in the development and expression of acquired resistance to lung disease is not wholly understood although they undoubtedly constitute the first line of defense against an aerogenic challenge. There is some controversy regarding the origin of these cells, as well as the nature of their response to infection, and their role in eliminating parasites capable of surviving and multiplying in an intracellular environment in the normal host. Studies will be conducted using parabiotic pairs of inbred rats and mice. Unilateral isotopic labeling of the macrophage precursors will be achieved with tritiated thymidine. The kinetics of the mononuclear and alveolar macrophage responses to both acute and chronic microbial infections following the introduction of selected intracellular parasites into the lung will be determined. The relationship of both alveolar and blood-borne macrophages in the establishment of the granulomatous response will be examined using a persisting microbial parasite. These kinetic studies will be extended to determine the fate of the inflammatory cells during the resolution of the infection as a result of the specific cellular immune response. The effect of T-cell depletion on the mobilization and expression of the immune response by both alveolar and immigrant macrophages will be examined, followed by appropriate T-cell restoration studies in an effort to determine the role of both macrophage populations in the pathogenesis of chronic lung disease, as well as in the ultimate resolution of the microbial infections, the repair of tissue damage and the ultimate restoration of a normal lung architecture and function. BIBLIOGRAPHIC REFERENCES: Collins, F.M. Mechanisms of adquired resistance to Pasteurella multocida infection: a review. Cornell Vet. 67, 103-138, 1977.